Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89±2.13%) with vesicle size of 144±3.47 nm (polydispersity index [PDI]=0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2±0.015% drug was released in 24 h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 μg/mL in plasma) was also maintained for at least 8 h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.     

Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8?±?18.69 to 797.7?±?12.45?nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC_0-48?hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.     

Preparation and evaluation of optimized zolmitriptan niosomal emulgel

Objective: Novel niosomal formulation may be successfully applied to treat a systemic disease such as migraine through transdermal drug delivery system (TDDS), moreover, the treatment of topical diseases such as mycotic infections by targeting and localizing the drug to the stratum corneum. The current study aims to formulate zolmitriptan (Zt) in niosomal vesicles to potentiate its transdermal effect.

Significance: The development of a promising niosomal formulation will push the scaling up of pharmaceutical industry in this field.

Methods: Design- Expert 10 was used to design twelve formulations using Box-Behnken. Zt loaded niosomes were prepared by the thin film hydration method using Span 60(S 60), Span 80(S 80) along with cholesterol(Ch) at three different levels. The optimized formulation (F11) was formulated in Emulgel (1:1 emulsion/gel ratio).

Results: The vesicles revealed vesicle size (VS) ranging from 133.1 to 851.3?nm, zeta potential (ZP) ?43.8 to ?82.8?mV, entrapment efficiency (EE%) from 66.7 to 88.7%, and Zt release after 4?h up to 67%. Optimized niosomal formulation (F11) depicted the smallest VS (133.1?nm), highest EE (88.7%), high ZP (?80.6?mV) and satisfactory release after 4?h (61.5%). There was a significant difference (p <.05) in drug permeation after 8?h for niosomal F11(460.98?ug/cm²) and niosomal F11 loaded Emulgel (336.92?ug/cm²) compared to plain Zt loaded emulgel (160.83?ug/cm²). Niosomal F11 loaded emulgel showed thixotropic behavior of rapid recovery, significant bioavailability and pharmacokinetic parameters as compared to the plain Zt-loaded Emulgel.

Conclusion: Optimized F11 represents a promising formulation for transdermal drug delivery system to treat both topical and systemic diseases.     

Development and evaluation of hollow mesoporous silica microspheres bearing on enhanced oral delivery of curcumin

The aim of this work is to develop curcumin-loaded hollow mesoporous silica microspheres (HMSMs@curcumin) to improve the poor oral bioavailability of curcumin. Hollow mesoporous silica microspheres (HMSMs) were synthesized in facile route using a hard template. HMSMs and HMSMs@curcumin were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption measurements, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). In addition, to demonstrate the potential application of the HMSMs@curcumin, cytotoxicity, in vitro release behavior and in vivo pharmacokinetics of curcumin loaded in these HMSMs were investigated by using of Caco-2 cells and Sprague-Dawley (SD) rats, respectively. These mono-dispersed HMSMs exhibited high drug loading ratio and encapsulation efficiency due to the mesoporous shell and hollow core. The excellent characteristics of HMSMs such as mono-dispersed morphology, smooth surface, uniform, ordered and size-narrowing mesopores resulted in a good in vitro release profile of curcumin from HMSMs@curcumin. Moreover, an impressive improvement in the oral absorption of curcumin and prolonged systemic circulation time were achieved in the in vivo animal studies. In addition, the good biocompatibility of developed HMSMs with Caco-2 cells was confirmed based on the in vitro cytotoxicity assay. In conclusion, this system demonstrated a great potential for efficient delivery of curcumin in vitro and in vivo, suggesting a good prospect for its application in clinic for therapeutic drug delivery in future.     

Artesunate-loaded chitosan/lecithin nanoparticles: Preparation,characterization, and in vivo studies

Artesunate (AST), the most widely used artemisnin derivative, has poor aqueous solubility and suffers from low oral bioavailability (~40%). Under these conditions, nanoparticles with controlled and sustained released properties can be a suitable solution for improving its biopharmaceuticals properties. This work reports the preparation and characterization of auto-assembled chitosan/lecithin nanoparticles loaded with AST and AST complexed with β-cyclodextrin (β-CD) to boost its antimalarial activity. The nanoparticles prepared by direct injection of lecithin alcoholic solution into chitosan/water solution have shown the particle size distribution below 300?nm. Drug entrapment efficiency was found to be maximum (90%) for nanoparticles containing 100?mg of AST. Transmission electron microscopy images show spherical shape with contrasted corona (chitosan) surrounded by a lipidic core (lecithin + isopropyl myristate). Differential scanning calorimeter thermograms demonstrated the presence of drug in drug-loaded nanoparticles along with the disappearance of decomposition exotherm suggesting the increased physical stability of drug in prepared formulations. Negligible changes in the characteristic peaks of drug in Fourier-transform infrared spectra indicated the absence of any interaction among the various components entrapped in the nanoparticle formulation. In vitro drug release behavior was found to be influenced by pH value. Increased in vivo antimalarial activity in terms of less mean percent parasitemia was observed in infected Plasmodium berghei mice after the oral administration of all the prepared nanoparticle formulations.     

Formulation and evaluation of thymoquinone niosomes: application of developed and validated RP-HPLC method in delivery system

Abstract

A rapid, accurate, and sensitive reverse phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the estimation of Thymoquinone (TMQ) in API as well as in noisome. The chromatograms were developed with the mobile phase – water: 2-propanol: methanol (50:45:5 v/v/v) as a solvent system at 254?nm. The method was validated as per ICH guidelines for different parameters and the recovery of TMQ was calculated in developed niosomes. Further, TMQ loaded niosomes (TMQNIOS) were prepared and evaluated for different parameters. The optimized TMQNIOS (F3) was further evaluated for surface morphology, in vitro drug release, permeation study, and confocal laser scanning microscopic (CLSM) study. The method showed linearity range between 6.25 and 100?µg/ml with low detection limit and quantitation limit with a value of 2.08 and 6.25?µg/ml. The developed formulations showed the vesicle size and encapsulation efficiency in the range of 157.32?±?3.15 to 211.44?±?5.23?nm and 59.32?±?4.87 to 83.21?±?3.55%, respectively. The drug release result showed the significant higher release from TMQNIOS in compared to TMQDIS, and the release kinetics data showed Higuchi's equation with highest regression coefficient values. The permeation study and the confocal laser microscopy study further confirmed the enhancement in permeation of TMQ in the intestinal mucosa.     

In vivo microdialysis for the evaluation of transfersomes as a novel transdermal delivery vehicle for cinnamic acid

In this study, cinnamic acid-loaded transfersomes were prepared and dermal microdialysis sampling was used in Sprague–Dawley rats to compare the amount of drug released into the skin using transfersomes as transdermal carriers with that released on using conventional liposomes. The formulation of cinnamic acid-loaded transfersomes was optimized by a uniform design through in vitro transdermal permeation studies. Hydration time was confirmed as a significant factor influencing the entrapment efficiency of transfersomes, further affecting their transdermal flux in vitro. The fluxes of cinnamic acid from transfersomes were all higher than those from conventional liposomes, and the flux from the optimal transfersome formulation was 3.01-fold higher than that from the conventional liposomes (p?in vivo microdialysis sampling method revealed that the dermal drug concentrations from transfersomes applied on various skin regions were much lower than those required with conventional liposomes. After the administration of drug-containing transfersomes and liposomes on abdominal skin regions of rats for a period of 10?h, the C_max of cinnamic acid from the compared liposomes was 3.21?±?0.25?μg/mL and that from the transfersomes was merely 0.59?±?0.02?μg/mL. The results suggest that transfersomes can be used as carriers to enhance the transdermal delivery of cinnamic acid, and that these vehicles may penetrate the skin in the complete form, given their significant deformability.     

In vitro comparative evaluation of monolayered multipolymeric films embedded with didanosine-loaded solid lipid nanoparticles: a potential buccal drug delivery system for ARV therapy

Drug delivery via the buccal route has emerged as a promising alternative to oral drug delivery. Didanosine (DDI) undergoes rapid degradation in the gastrointestinal tract, has a short half-life and low oral bioavailability, making DDI a suitable candidate for buccal delivery. Recent developments in buccal drug delivery show an increased interest toward nano-enabled delivery systems. The advantages of buccal drug delivery can be combined with that of nanoparticulate delivery systems to provide a superior delivery system. The aim of this study was to design and evaluate the preparation of novel nano-enabled films for buccal delivery of DDI. Solid lipid nanoparticles (SLNs) were prepared via hot homogenization followed by ultrasonication and were characterized before being incorporated into nano-enabled monolayered multipolymeric films (MMFs). Glyceryl tripalmitate with Poloxamer 188 was identified as most suitable for the preparation of DDI-loaded SLNs. SLNs with desired particle size (PS) (201?nm), polydispersity index (PDI) (0.168) and zeta potential (?18.8?mV) were incorporated into MMFs and characterized. Conventional and nano-enabled MMFs were prepared via solvent casting/evaporation using Eudragit RS100 and hydroxypropyl methylcellulose. Drug release from the nano-enabled films was found to be faster (56% versus 20% in first hour). Conventional MMFs exhibited higher mucoadhesion and mechanical strength than nano-enabled MMFs. SLNs did not adversely affect the steady state flux (71.63?±?13.54?µg/cm²?h versus 74.39?±?15.95?µg/cm²?h) thereby confirming the potential transbuccal delivery of DDI using nano-enabled MMFs. Nano-enabled buccal films for delivery of DDI can be successfully prepared, and these physico-mechanical studies serve as a platform for future formulation optimization work in this emerging field.     

Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole

Clotrimazole, which is an imidazole derivative antifungal agent, was widely used for the treatment of mycotic infections of the genitourinary tract. To develop alternative formulation for the vaginal administration of clotrimazole to provide sustained and controlled release of appropriate drug for local vaginal therapy, liposomes/niosomes were evaluated as delivery vehicles. To optimize the preparation of liposomes/niosomes with regard to size and entrapment efficiency, multilamellar liposomes/niosomes containing drug were prepared by lipid hydration method. The prepared liposomes/niosomes were incorporated into 2% carbopol gel, and the systems were evaluated for drug stability in phosphate-buffered saline (pH 7.4) and simulated vaginal fluid at 37 +/- 1 degrees C. Further, the vesicle gel system was evaluated by antifungal activity and tolerability on tissue level in rat.     

Natamycin niosomes as a promising ocular nanosized delivery system with ketorolac tromethamine for dual effects for treatment of candida rabbit keratitis; in vitro/in vivo and histopathological studies

Objectives: This study was aimed to develop dual-purpose natamycin (NAT)-loaded niosomes in ketorolac tromethamine (KT) gels topical ocular drug delivery system to improve the clinical efficacy of natamycin through enhancing its penetration through corneal tissue and reducing inflammation associated with Fungal keratitis (FK).

Significance: Nanosized carrier systems, as niosomes would provide great potential for improving NAT ocular bioavailability.NAT niosomal dispersion formulae were prepared and then incorporated in 0.5%KT gels using different mucoadhesive viscosifying polymers.

Methods: Niosomes were prepared using the reverse-phase evaporation technique. In vitro experimental, and in vivo clinical evaluations for these formulations were done for assessment of their safety and efficacy for treatment of Candida Keratitis in Rabbits. In vitro release study was carried out by the dialysis method. In vivo and histopathological studies were performed on albino rabbits.

Results: NAT niosomes exhibited high entrapment efficiency percentage (E.E%) up to96.43% and particle size diameter ranging from 181.75?±?0.64 to 498.95?±?0.64?nm, with negatively charged zeta potential (ZP). NAT niosomal dispersion exhibited prolonged in vitro drug release (40.96–77.49% over 24h). NAT-loaded niosomes/0.5%KT gel formulae revealed retardation in vitro release, compared to marketed-product (NATACYN^®) and NAT-loaded niosomes up to57.32% (F8). In vivo experimental studies showed the superiority for F8 in treatment of candida keratitis and better results on corneal infiltration and hypopyon level. These results were consistent with histopathological examination in comparison with F5 and combined marketed products (NATACYN^® and Ketoroline^®).

Conclusions: This study showed that F8 has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application and enhancing the prolonged delivery of NAT and penetrating the cornea tissues.     

Preparation and evaluation of lyophilized liposome-encapsulated bufadienolides

Objective: The objective of this study was to prepare bufadienolides-loaded liposome (BU-lipo). Methods: The BU-lipo was prepared by a thin-film hydration method involving sonication and lyophilization procedures. The lyophilized BU-lipo was characterized with regard to the appearance and particle size by scanning electron microscopy, transmission electron microscopy, and photon correlation spectroscopy. The entrapment efficiency (EE) of BU-lipo was evaluated by the microdialysis technique. Results: In the optimal formulation, Lipoid E-80® and the mass ratio of cholesterol to lipid were fixed at 1.25% and 0.05. The media diameters of BU-lipo before and after lyophilization were about 100 nm, and the EEs of bufalin (B), cinobufagin (C), and resibufogenin (R) were 86.5%, 90.0%, and 92.1%, respectively. In the EE study, the probe recoveries of B, C, and R were 21.53?±?1.14%, 19.49?±?1.34%, and 20.19?±?1.25%, respectively, at a flow rate of 4 μL/min by the gain method. The EE of BU-lipo evaluated by microdialysis and ultrafiltration were equivalent. Conclusion: The lyophilized BU-lipo contained trehalose (10%) was stable up to 6 months in a desiccator under 2ºC–8ºC. The microdialysis technique has a wide application perspective in the investigation of the free-drug concentration of microcarrier systems.     

Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery

A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2?min; floating duration > 10?h) and satisfactory drug-release profiles (immediate release of CET in 10?min and sustained release of BN for 12?h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5?h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN’s absorption at its absorption site and the efficacy of both CET and BN.     

Preparation of multiparticulate systems for oral delivery of a micronized or nanosized poorly soluble drug

The purpose of the present work was to prepare multiparticulate drug delivery systems for oral administration of a poorly soluble drug such as itraconazole. Multiparticulate systems were prepared by extrusion/spheronization technique using a mix of crospovidone, low viscosity hypromellose, microcrystalline cellulose, micronized drug and water. In order to improve the release performance of the multiparticulate systems, the micronized drug was suspended in water with polysorbate 20 and nanonized by a high-pressure homogenization. The suspension of drug nanoparticles was then spray-dried for enabling an easy handling of the drug and for preventing the over-wetting of the powders during extrusion/spheronization processing. Both multiparticulate units prepared with micronized or nanonized drug showed acceptable disintegrating properties. The nanosizing of micronized drug powder provided a significant improvement of drug dissolution rates of the multiparticulates.     

Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride

The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Berberine hydrochloride (BBH), an important bioactive compound from Chinese Medicines with poor water solubility. Pseudoternary phase diagrams were constructed using oil, surfactant and co-surfactant types to identify the efficient self-microemulsification region. SMEDDS was characterized by morphological observation, droplet size, zeta-potential determination, stability, in vitro release and in vivo bioavailability study. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 40% (w/w) of ethyl linoleate and oleic acid (2:1), 35% (w/w) Tween-80 and 25% (w/w) glycerol. The SMEDDS of BBH could exhibit good stability. In vitro release test showed a complete release of BBH from SMEDDS was in 5 h. In vivo results indicated that the peak plasma concentration (C_max) and the area under the curve (AUC_{0→12 h}) of SMEDDS of BBH were higher than the commercial tablet by 163.4% and 154.2%, respectively. The relative bioavailability of SMEDDS of BBH was enhanced about 2.42-fold compared with the commercial tablet in rats. The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability.     

Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin

Context: Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs.

Objectives: This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability.

Methods: Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug–excipient interaction using zetasizer, atomic force microscope (AFM), LC–MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits.

Results: The vesicles were spherical with 247?±?4.67?nm diameter hosting 73.29?±?3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80?±?0.51% hemolysis at 1000?µg/mL. It was also found safe in mice up to 2.5?g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits.

Conclusions: The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.     

Electroporation of polymeric nanoparticles: an alternative technique for transdermal delivery of insulin

Purpose: The aim was to study transdermal electroporation of insulin-loaded nanocarriers as a methodology for delivering macromolecules. Methods: The efficacy of electroporation of insulin as solution and nanoparticles was compared in vitro and in vivo. Histology and confocal laser scanning microscopy were used to assess the effects of electroporation on skin structure, whereas the latter also demonstrated the depth of permeation of the nanoparticles. In vivo studies were performed on streptozotocin-diabetic male Wistar rats and compared with subcutaneous administration. Results: A linear increase in insulin flux was noted on increasing the applied voltage (R² = 0.9514), the number of pulses (R² = 0.8515), and the pulse length (R² = 0.9937). Electroporation of nanoparticles resulted in fourfold enhancement in insulin deposition in rat skin in contrast to solution. In vivo studies showed maximum reduction of 77 ± 5% (87.2 ± 6.4 mIU/mL, t = 2 hours) and 85 ± 8% (37.8 ± 10.2 mIU/mL, t = 4 hours) in blood glucose levels for solution and nanoparticles, respectively, with therapeutic levels maintained for 24 and 36 hours. Conclusion: Overall, electroporation of polymeric nanosystems proved to be an ideal alternative to injectable administration.     

Development and in vitro evaluation of alginate gel-encapsulated, chitosan-coated ceramic nanocores for oral delivery of enzyme

The successful administration of protein and peptide drugs by oral route maintaining their active conformation remains a key challenge in the field of pharmaceutical technology. In the present study, we propose the use of a nanosize ceramic core-based system for effective oral delivery of acid-labile model enzyme, serratiopeptidase (STP). Ceramic core was prepared by colloidal precipitation and sonication of disodium hydrogen phosphate solution and calcium chloride solution at room temperature. The core was coated with chitosan under constant stirring and Fourier-Transform Infra Red Spectroscopy (FTIR) confirmed phosphoric groups of calcium phosphate linked with ammonium groups of chitosan in the nanoparticles; then the enzyme was adsorbed over the preformed nanocore. Protein-loaded nanocore was further encapsulated into alginate gel for enzyme protection. Prepared system was characterized for size, shape, loading efficiency, and in vitro release profile (pH 1.2 and pH 7.4). The effect of processing variables on the size of the core was evaluated to form small, uniform, and discrete nanocores. Stability and integrity of enzyme during processing steps was assessed by in vitro proteolytic activity. The prepared system was examined to be spherical in shape with diameter 925 ± 6.81 nm using TEM. The in vitro release data followed the Higuchi model, showing a low amount (26% ± 2.4%) of diffusion-controlled drug release (R² = 0.9429) in acidic buffer up to a period of 2 to 6 hours, signifying the integrity of alginate gel in acid. In the alkaline medium sustained and nearly complete first order release of protein was observed up to a 6 hours. It is inferred that the protein-loaded ceramic core acts as a reservoir of the adsorbed enzyme and alginate gel provides protection to STP for controlled release in intestinal pH when compared to the enzyme solution.     

Critical evaluation of permeation enhancers for oral mucosal drug delivery

Background: Drug delivery via oral mucosa is an alternative method of systemic administration for various classes of therapeutic agents. Among the oral mucosae, buccal and sublingual mucosae are the primary focus for drug delivery. Buccal delivery offers a clear advantage over the peroral route by avoidance of intestinal and hepatic first-pass metabolism. However, despite offering the possibility of improved systemic drug delivery, buccal administration has been utilized for relatively few pharmaceutical products so far. One of the major limitations associated with buccal delivery is low permeation of therapeutic agents across the mucosa. Various substances have been explored as permeation enhancers to increase the flux/absorption of drugs through the mucosa, but irritation, membrane damage, and toxicity are always associated with them and limit their use. A clinically accepted permeation enhancer must increase membrane permeability without causing toxicity and permanent membrane damage. To date, the information available on oral mucosal permeation enhancement is much less than transdermal enhancement, though oral mucosa is more resistant to damage than other mucosal membranes. This article reviews the various categories of permeation enhancers for oral mucosal drug delivery, their mechanism of action, their usefulness, and the limitations associated with their use. Conclusion: To optimize the concentration of enhancer to limit its toxicity while facilitating an enhancing effect reproducibly will be a big challenge for future developments. Advances in permeability modulation and formulation with appropriate enhancers can provide for effective and feasible buccal drug delivery for many drugs, which otherwise have to be injected or ingested with water.     

Development and in vitro evaluation of oxytetracycline‐loaded PMMA nanoparticles for oral delivery against anaplasmosis

Poly‐methyl methacrylate (PMMA) polymer with remarkable properties and merits are being preferred in various biomedical applications due to its biocompatibility, non‐toxicity and cost effectiveness. In this investigation, oxytetracycline‐loaded PMMA nanoparticles were prepared using nano‐precipitation method for the treatment of anaplasmosis. The prepared nanoparticles were characterised using dynamic light scattering (DLS), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The mean average diameter of the nanoparticles ranged between 190–240 nm and zeta potential was found to be −19 mV. The drug loading capacity and entrapment efficiency of nanoparticles was found varied between 33.7–62.2% and 40.5–60.0%. The in vitro drug release profile exhibited a biphasic phenomenon indicating controlled drug release. The uptake of coumarin‐6(C‐6)‐loaded PMMA nanoparticles in Plasmodium falciparum (Pf 3D7) culture model was studied. The preferential uptake of C‐6‐loaded nanoparticles by the Plasmodium infected erythrocytes in comparison with the uninfected erythrocytes was observed under fluorescence microscopy. These findings suggest that oxytetracycline‐loaded PMMA nanoparticles were found to be an effective oral delivery vehicle and an alternative pharmaceutical formulation in anaplasmosis treatment, too.Inspec keywords: nanoparticles, nanomedicine, conducting polymers, microorganisms, cellular biophysics, toxicology, drug delivery systems, light scattering, atomic force microscopy, differential scanning calorimetry, Fourier transform infrared spectra, bloodOther keywords: in vitro evaluation, oxytetracycline‐loaded PMMA nanoparticles, anaplasmosis, polymethyl methacrylate polymer, biocompatibility, toxicity, oxytetracycline‐nanoparticles, nanoprecipitation method, dynamic light scattering, atomic force microscopy, AFM, differential scanning calorimetry, DSC, Fourier transform infrared spectroscopy, FTIR spectroscopy, zeta potential, drug loading capacity, entrapment efficiency, in vitro drug release profile, biphasic phenomenon, coumarin‐6(C‐6)‐loaded PMMA nanoparticles, plasmodium falciparum culture model, preferential uptake, plasmodium infected erythrocytes, fluorescence microscopy, oral delivery vehicle, anaplasmosis treatment, size 190 nm to 240 nm     

Development of Monolithic Osmotic Pump Tablet System for Isosorbide-5-Mononitrate Delivery and Evaluation of it In Vitro and In Vivo

The objective of this study is to develop the monolithic osmotic pump tablet system (MOTS) containing isosorbide-5-mononitrate (5-ISMN), and to evaluate its in vitro and in vivo properties. The influences of tablet formulation variables, size and location of the delivery orifice, membrane variables, and pH value of the dissolution medium on 5-ISMN release from MOTS have been investigated. These results demonstrated that the tablet core played an important role in MOTS, and membrane variables could affect the 5-ISMN release rate. The optimal formulation of 5-ISMN MOTS was determined by uniform design. Furthermore, the dog pharmacokinetics and relative bioavailability of the test formulation (5-ISMN MOTS) have been compared with the reference formulation (Imdur^®: 60 mg/tablet, a sustained release, SR, tablet system) following an oral single dose of 60 mg given to each of six Beagle dogs. The mean drug fraction absorbed by the dog was calculated by the Wagner–Nelson technique. The results showed that drug concentration in plasma could be maintained more stable and longer after the administration of 5-ISMN MOTS compared with the matrix tablets of Imdur^®, and a level A “in vitro–in vivo correlation” was observed between the percentage released in vitro and percentage absorbed in vivo. It is concluded that 5-ISMN MOTS is more feasible for a long-acting preparation than 5-ISMN SR tablet system as once-a-day treatment, and it is very simple in preparation, and can release 5-ISMN at the rate of approximately zero order for the combination of hydroxypropylmethyl cellulose as retarder and NaCl as osmogent.